The atomic force microscope (AFM) can be used to detect and measure interactions between and within molecules. Key to this process is the ability to construct AFM probes with defined chemical and biomolecular properties. In Phase I we developed advanced methods for construction of these probes using an infra-red (IR) laser trap (optical tweezers) to spot weld microparticles onto AFM probes. A method for initiating sample probe interactions with minimal damage to the probe was developed. A novel and very useful type of modified AFM probe with an apical aperture (ApTip) was invented. In Phase II ApTips will be used for mounting very small biologically or chemically active microparticles, thereby expanding the repertoire of sizes of functionalized tips. ApTips will also be employed in the development of techniques for construction of patterned arrays of biomolecules (BioArrays). Photopatterning and photocrosslinking methods will be tested as well. Sophisticated surface interrogation methods will be developed for scanning BioArrays with functionalized AFM probes. The product of these efforts will be a novel and powerful technology using modified AFM probes for rapid identification and analysis of defined molecular interactions between surface immobilized molecules. PROPOSED COMMERCIAL APPLICATION: Modified AFM probes and BioArrays have commercial applications in genome analysis, drug discovery, nanobiolithography, immuno and nucleic acid diagnostics. These tools provide a high throughput and extremely sensitive technology for molecular screening and characterization.